RESUMEN
AIMS: The relationship between the coronary artery running pattern and development of coronary lesions was re-examined herein using WHHLMI rabbits, an animal model of spontaneous coronary atherosclerosis. METHODS: The coronary artery running pattern was analyzed using an X-ray computed tomography (CT) apparatus after perfusion. Pathological sections were prepared (Victoria blue-HE staining) at 100 µm intervals from the origin of the left circumflex artery (LCX). The severity of coronary lesions was evaluated based on cross-sectional narrowing (lesion area/inner area of the internal elastic lamina). RESULTS: In the CT analysis, the angle of the main curvature of the LCX negatively correlated with the percentage of sections with lesions and cross-sectional narrowing. The percentage of sections with lesions was significantly higher in acute angle-type LCX than in obtuse angle-type LCX. Cross-sectional narrowing was also significantly greater in acute angle-type LCX than in obtuse angle-type LCX. The percentage of fibrous lesions was high at the proximal region of LCX, whereas that of lipid-rich lesions was high at the curvature. In 24 months age group, the percentage of sections with calcification in acute angle-type LCX was about twice that in obtuse angle-type LCX. CONCLUSIONS: Individual differences were observed in the angle of the main curvature of the LCX, which affected the occurrence and extension of atherosclerotic lesions.
Asunto(s)
Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/patología , Modelos Animales de Enfermedad , Hipercolesterolemia/fisiopatología , Índice de Severidad de la Enfermedad , Animales , Enfermedad de la Arteria Coronaria/etiología , Progresión de la Enfermedad , Femenino , Hipercolesterolemia/complicaciones , Masculino , Conejos , Factores de RiesgoRESUMEN
BACKGROUND AND AIMS: Aortic valve stenosis (AS) is the most common valvular heart disease and can be life-threatening. The pathogenesis of aortic valve calcification remains largely unknown, primarily due to the lack of an adequate animal model. The high-cholesterol diet-induced AS model in rabbits is one of the established models, but it has the significant limitation of liver dysfunction leading to low survival rates. We hypothesized that a myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbit, an animal model of familial hypercholesterolemia and atherosclerosis, is a useful animal model of AS. METHODS: WHHLMI rabbits, aged 20 months and 30 months (nâ¯=â¯19), and control Japanese White rabbits (nâ¯=â¯4), aged 30 months, were used and evaluated by echocardiography under anesthesia. Pathological evaluation and quantitative analyses by polymerase chain reaction (PCR) were also performed. RESULTS: The lipid profile was similar between 20 months and 30 months. Two rabbits died due to spontaneous myocardial infarction during the study. Thirty-month-old WHHLMI rabbits exhibited significantly smaller aortic valve area (0.22⯱â¯0.006â¯cm2vs. 0.12⯱â¯0.01â¯cm2, pâ¯<â¯0.05) and higher maximal transvalvular pressure gradient (7.0⯱â¯0.32 vs. 9.9⯱â¯0.95â¯mmHg, pâ¯<â¯0.05) than 20 month-old rabbits. Macroscopic examination of excised aortic valves demonstrated thickened and degenerated valve leaflets at 30 months. Histological evaluation confirmed thickened leaflets with calcified nodules at 30 months. Real-time PCR of resected aortic valve also showed increased expression level of calcification-related molecules including osteopontin, Sox9, Bmp2, RANKL, osteoprotegerin, and Runx2 (pâ¯<â¯0.05 each) in 30-month-old rabbits. CONCLUSIONS: WHHLMI rabbits may be useful models of early-stage AS in vivo.